Small biparietal diameter and head circumference are part of the phenotype instead of independent prognostic markers in fetuses with spinal dysraphism.

OBJECTIVE: The aim of this retrospective study was to assess the fetal biparietal diameter (BPD) and head circumference (HC) in the second trimester of pregnancy in fetuses with open spinal dysraphism. METHODS: BPD and HC were measured at 16-26 weeks in 74 fetuses with open spinal dysraphism and compared with reference values. RESULTS: BPD was smaller in fetuses with open spinal dysraphism. Of all cases with open spinal dysraphism, 62.2% had a BPD <3rd percentile and 79.7% had a BPD <10th percentile. Of all patients, 54.1% had an HC <3rd percentile and 74.3% had an HC <10th percentile. CONCLUSION: Almost all fetuses with open neural tube defects have a smaller BPD and HC at 16-26 weeks compared with reference values, which implicates that this is part of the phenotype of children with open spinal dysraphism instead of an independent prognostic marker for a poor cognitive outcome.

Motor evoked potentials and compound muscle action potentials as prognostic tools for neonates with spina bifida.

UNLABELLED: MEPs and CMAPs as prognostic tools for spina bifida. AIM: The aim of this prospective study was to determine the prognostic value of neurophysiological investigations compared to clinical neurological examination in infants with spina bifida. METHODS: Thirty-six neonates born with spina bifida between 2002 and 2007 were evaluated and followed for 2 years. Lumbar motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were obtained at the median age of 2 days old before surgical closure of the spinal anomaly. MEPs were recorded from the quadriceps femoris, tibialis anterior, and gastrocnemius muscles and CMAPs from the latter two muscles. Areas under the curve and latencies of the MEPs and CMAPs were measured. Clinical neurological outcome at the age of 2 years was described using Muscle Function Classes (MFCs) and ambulation status. RESULTS: The areas under the curve of MEPs and CMAPs in the legs were associated with lower neonatal levels of motor and sensory impairment. Better muscle function class of the lower limbs at 2 years of age was associated with larger MEP and CMAP areas of the gastrocnemius and tibialis anterior muscles at neonatal age. DISCUSSION: MEPs and CMAPs of the gastrocnemius and tibialis anterior muscles are of prognostic value for clinical neurological outcome in neonates born with spina bifida.

Motor sequence learning in children with spina bifida.

Cognitive and motor problems are common in children with spina bifida (SB), particularly in those children with cerebral malformations (SBM). Little is known about how these conditions affect motor learning. This study examines motor sequence learning in children with SB, SBM, and healthy controls. Assessment consisted of neuropsychological tests, a simple drawing task, and a spatial motor sequence learning task. Implicit motor learning was unaffected in children with SB(M), and their sequence learning ability was also similar to that of controls. However, both groups (SB and SBM) showed impaired motor performance. The role of cerebellar malformation with SB(M) is discussed.

Contribution of the corticospinal tract to motor impairment in spina bifida.

We aimed to disentangle the proportional contributions of upper and lower motor neuron dysfunction to motor impairment in children with spina bifida. We enrolled 42 children (mean age, 11.2 years; standard deviation, 2.8 years) with spina bifida and 36 control children (mean age, 11.4 years; standard deviation, 2.6 years). Motor impairment was graded to severity scales in children with spina bifida. We recorded motor evoked potentials after transcranial and lumbosacral magnetic stimulation and compound muscle action potentials after electric nerve stimulation. Regarding lower motor neuron function, severely impaired children with spina bifida demonstrated smaller compound muscle action potential areas and lumbosacral motor evoked potential areas than control children; mildly impaired children hardly differed from control children. Compound muscle action potential latencies and lumbosacral motor evoked potential latencies did not differ between children with spina bifida and control children. Regarding upper motor neuron function, children with spina bifida demonstrated smaller transcranial motor evoked potential areas and longer central motor conduction times than control children. The smallest motor evoked potential areas and longest central motor conduction times were observed in severely impaired children. In children with spina bifida, the contribution of upper motor neuron dysfunction to motor impairment is more considerable than expected from clinical neurologic examination.

Essential features of Chiari II malformation in MR imaging: an interobserver reliability study--part 1.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features of the malformation on MR images may not always be straightforward. In an attempt to select those features that unambiguously characterize the Chiari II malformation, we investigated the interobserver reliability of all its well-known MR features. METHODS: Brain MR images of 79 children [26 presumed to have Chiari II malformation, 36 presumed to have no cerebral abnormalities, and 17 children in whom some Chiari II malformation features might be present; mean age 10.6 (SD 3.2; range, 6-16) years] were blindly and independently reviewed by three observers. They rated 33 morphological features of the Chiari II malformation as present, absent, or indefinable in three planes (sagittal, axial, and coronal). The interobserver reliability was assessed using κ statistics. RESULTS: Twenty-three of the features studied turned out to be unreliable, whereas the interobserver agreement was almost perfect (κ value > 0.8) for nine features (eight in the sagittal plane and one in the axial plane, but none in the coronal plane). CONCLUSIONS: This study presents essential features of the Chiari II malformation on MR images by ruling out the unreliable features. Using these features may improve the assessment of Chiari II malformation in clinical and research settings.

Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging--part 2.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings.

Clinical practice: swallowing problems in cerebral palsy.

Cerebral palsy (CP) is the most common physical disability in early childhood. The worldwide prevalence of CP is approximately 2-2.5 per 1,000 live births. It has been clinically defined as a group of motor, cognitive, and perceptive impairments secondary to a non-progressive defect or lesion of the developing brain. Children with CP can have swallowing problems with severe drooling as one of the consequences. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Early attention should be given to dysphagia and excessive drooling and their substantial contribution to the burden of a child with CP and his/her family. This review displays the important functional and anatomical issues related to swallowing problems in children with CP based on relevant literature and expert opinion. Furthermore, based on our experience, we describe a plan for approach of investigation and treatment of swallowing problems in cerebral palsy.

What could predict effectiveness of Botulinum Toxin to treat drooling: a search for evidence of discriminatory factors on the level of body functions or structures.

BACKGROUND: The treatment of drooling is important to families that experience the daily impact and research to elucidate clinical factors that play a role in the outcome of drooling treatment should be encouraged. AIM: To define clinical factors that influence therapy outcome of submandibular Botulinum Toxin (BoNT-A) injections for drooling. METHODS: Prospectively collected data of 128 children with cerebral palsy were evaluated; 80 spastic and 48 dyskinetic movement disorder, mostly Gross Motor Function Classification System III and higher; over 70% had an IQ <70. In addition, 23 fully ambulant children with exclusively intellectual disability were treated for drooling by ultrasound-guided injections of BoNT-A into the submandibular glands. Salivary flow rates and drooling quotients were measured at baseline and at 8 weeks after injection. Extensive information about the oral motor performance was gathered. Successful clinical response was defined as a 50% reduction of the baseline Drooling Quotient; 85 children were responsive to BoNT-A and 66 children unresponsive. RESULTS: Five nominated clinical factors that possibly could influence saliva reduction (head position, lip seal, voluntary control over the tongue, control of voluntary movement functions, and mental age) did not influence the responsiveness to BoNT-A. INTERPRETATION: Other variables need to be considered to predict the outcome of BoNT-A treatment. This article describes the first attempt to reveal the contribution of body functions and structures to the outcome of BoNT-A submandibular injections.

Does motor performance matter in botulinum toxin efficacy for drooling?

The aim of this study was to define factors that influence therapy outcome of submandibular botulinum toxin injections for drooling in children with cerebral palsy or mental disability. We postulated that differences in response may be explained by the variation of dysfunctions in the various cerebral palsy subtypes. Prospectively collected data were evaluated of 80 spastic and 48 dyskinetic children, of whom 70% had an IQ of <70. In addition, the data of 23 fully ambulant children with mental disability only were examined. Flow and Drooling Quotient were assessed at baseline and at 8 weeks after injection. After treatment, both the Drooling Quotient and submandibular flow decreased in all children. Morbidity associated with the procedure was limited. Ninety-three children responded to botulinum. Decrease of submandibular flow in these children was associated with reduction of parotid flow. In those who did not respond to therapy, spread across all 3 diagnostic classifications, parotid flow increased after injection. Response failure is characterized by increased parotid flow after injection; however, the precise role of parotid flow in therapy failure remains unclear. We cannot predict who will respond to botulinum toxin to treat drooling.

Influence of birth mode on early neurological outcome in infants with myelomeningocele.

OBJECTIVE: The aim of the study was to determine whether route of birth affects early neurological outcome in infants with myelomeningocele. STUDY DESIGN: In a retrospective cohort study, 95 neonates with myelomeningocele evaluated at the Radboud University Nijmegen Medical Centre between 1990 and 2006 were reviewed. The effect of delivery mode on early neurological outcome was assessed as the difference between the functional neurological level of the defect and the X-ray level (ΔFAX). RESULTS: Early neurological outcome was better in the vaginally delivered infants (ΔFAX 0.96 ± 2.1) than in those delivered by cesarean section (ΔFAX 0.20 ± 2.5). After correction for confounders, multiple regression analysis demonstrated that vaginal delivery was associated with significantly better early neurological outcome as compared to cesarean section (ß=1.21; 95% CI 0.16; 2.27; p=0.03) for infants in vertex and breech position combined. Subgroup analysis revealed a non-significant trend towards better outcome after vaginal delivery that was more pronounced in infants in breech position than in vertex position. CONCLUSION: In infants with myelomeningocele, born in either vertex or breech position, there is no clinical evidence that early neurological outcome is improved by cesarean section.

Botulinum toxin versus submandibular duct relocation for severe drooling.

AIM: Botulinum neurotoxin type A (BoNT-A) has been described as an effective intervention for drooling and is being increasingly adopted. However, its effectiveness compared with established treatments is still unknown. We undertook a within-participants observational study to examine this. METHOD: An historic cohort was formed of 19 children and young adults (10 males, nine females) with severe drooling who underwent BoNT-A injections followed by surgical re-routing of the submandibular duct at least 6 months later. Mean age at time of admission was 11 years 5 months (range 5-17 y) and mean age at the time of surgery was 14 years (range 6-23 y). Fifteen children were diagnosed with bilateral cerebral palsy (CP), three with unilateral CP, and one with non-progressive developmental delay. Gross Motor Function Classification System levels were the following: level I, n=1; level II, n=2; level III, n=7; level IV, n=6; and level V, n=3). The primary outcome was the drooling quotient, which was assessed before each intervention and 8 and 32 weeks thereafter. A multivariate analysis of variance of repeated measures was performed, with the measurement points as the within-participant variables. RESULTS: The drooling quotient was reduced to a greater extent after surgery than after BoNT-A administration (p=0.001). Compared with a baseline value of 28, the mean drooling quotient 8 weeks after surgery was 10, and 32 weeks after surgery was 4 (p<0.001). Among the group treated with BoNT-A, the drooling quotient showed a significant reduction from a baseline value of 30 to 18 after 8 weeks (p=0.02), and a continued but diminished effect after 32 weeks (drooling quotient 22; p=0.05). INTERPRETATION: Both interventions are effective, but surgery provides a larger and longer-lasting effect.

Thickened saliva after effective management of drooling with botulinum toxin A.

AIM: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. METHOD: We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ<70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT-A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT-A treatment. RESULTS: Both submandibular salivary flow rate (baseline 0.38 mL/min; 24 wks after injection 0.26 mL/min) and drooling quotient (baseline 42.5%; 24 wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830 U/mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. INTERPRETATION: When making decisions about the use of BoNT-A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT-A treatment should be taken into account.

Motor profile and cognitive functioning in children with spina bifida.

BACKGROUND: Spina bifida is a complex neuroembryological disorder resulting from incomplete closure of the posterior neural tube. Morbidity in the different fields of motor and cognitive neurodevelopment is variable in nature and severity, and often hard to predict. AIMS: The current study investigates the relationship between cognitive functioning, fine motor performance and motor quality in children with spina bifida myelomeningocele (SBM) and SB-only, taking into consideration the cerebral malformations. MATERIAL AND METHODS: Forty-one children were included (22 girls and 19 boys aged between 6 and 14 years, mean age 10;0 years) in the study. A comprehensive assessment was conducted of cognitive functioning and motor profile, including fine motor and visual-motor functioning, and motor quality. The performance outcomes were analyzed for the total group of children and separately for the nonretarded children (FSIQ> or =70, N=30) to eliminate the influence of global intellectual impairment. RESULTS: Although the children with spina bifida showed increased incidence of cognitive and fine motor impairment, and impaired motor quality, after exclusion of the overall retarded children no associations were found between cognitive functioning and motor profile. In the comparison of SBM to SB-only specific differences were found for performance IQ, visual-motor functioning and motor quality, but not fine motor functioning. CONCLUSION: Our findings underscore the role of cerebral malformation in spina bifida and its consequences for neuropsychological functioning. The complicated developmental interactions found strengthen the need for an individualized management of children with SB.

Neuropsychological assessment of attention in children with spina bifida.

BACKGROUND: Children with the severe form of spina bifida (SBM: spina bifida with myelomeningocele with accompanying hydrocephalus) may manifest attention deficits, and have a similar psychological profile to children with hydrocephalus due to other etiologies. It is unclear to what extent tests to assess attention in SBM are confounded by the accompanying cognitive or visual-motor impairments. The aim of this study was to analyse attention functions by administering two different types of attention tests, one with high and the other with low cognitive and motor requirements. This enabled the possible interaction between attention and cognitive and motor impairment to be assessed. METHODS: The study group comprised 31 children with SBM with shunted hydrocephalus. Twenty children with SB-only formed a closely matched comparison group. Of these, 19 children with SBM and 18 with SB had a full-scale IQ (FSIQ) higher than 70. All had undergone spinal surgery and all children with SBM had been shunted within the first months of life. Between 6 and 15 years of age, the children were assessed on focused and sustained attention, encoding, and distractibility/impulsivity, using both traditional tests and computerized attention tests. RESULTS: Compared to the SB group, attention scores of children with SBM were lower on the traditional tests, but when interfering cognitive and visual-motor requirements were eliminated using the computerised tasks, most differences disappeared. Furthermore, in contrast to traditional attention tasks, computerized tests showed no significant correlations with IQ-scores and visual-motor skills. CONCLUSION: Assessment of attention functions in children with SBM by traditional tests may be misleading, because this paediatric population with complex cerebral malformations has difficulty with the cognitive and visual-motor requirements. To control for these interactions, the use of both traditional and computerized attention tests is recommended.

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

AIM: To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation. METHOD: Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled (57 males, mean age 9y 5mo [3y 11mo], range 3-19y; 43 females, mean age 10y 1mo [4y 9mo], range 4-19y), of whom 53 had spastic, 42 had dyskinetic, and five had ataxic CP. Almost all children were affected bilaterally, and 90 of them were at Gross Motor Function Classification System levels III or higher. The saliva was collected by the swab saliva collection method. The intensity of drooling was evaluated using the drooling quotient. RESULTS: No difference was found in the flow rates, age, or sex between healthy children and children with CP who drooled. On additional subgroup analysis, the flow rates of children with dyskinetic CP differed statistically from those of healthy children (submandibular p=0.047, parotid p=0.040). INTERPRETATION: This study supports the finding in previous studies that no hypersalivation exists in children with CP who drool. Dysfunctional oral motor control seems to be responsible for saliva overflow from the mouth, whereas increased unstimulated salivary flow may occur in children with dyskinetic CP as a result of hyperkinetic oral movements.

Compound muscle action potentials in newborn infants with spina bifida.

The aim of this study was to investigate the relationship between compound muscle action potentials (CMAPs) and neurological impairment in newborn infants with spina bifida. Thirty-one newborn infants (17 males, 14 females, mean gestational age 39 wks [SD 2]; mean birthweight 3336 g [SD 496]) with spina bifida were investigated at a median age of 2 days (range 1-18 d). Motor and sensory impairment and muscle stretch reflexes were assessed and neuroimaging was performed. CMAPs were recorded from the tibialis anterior muscle and the gastrocnemius muscle after percutaneous electrical nerve stimulation. CMAPs were obtained in almost all infants. The area under the curve of the CMAP (CMAP-area) was associated with motor and sensory impairment and with the presence of muscle stretch reflexes, but not with the morphological level of the spinal anomaly. These associations were stronger for the gastrocnemius muscle than for the tibialis anterior muscle. In conclusion, the CMAP-area correlates with neurological impairment in neonatal spina bifida and provides an estimate of residual motor neuron function in affected spinal segments. The assessment of CMAPs after percutaneous electrical nerve stimulation is recommended as an additional instrument to the clinical neurological examination and imaging studies.

Rituximab and intravenous immunoglobulins for relapsing postinfectious opsoclonus-myoclonus syndrome.

We describe 2 children with postinfectious opsoclonus-myoclonus syndrome. Although the patients initially responded to monotherapy with methylprednisolone, intravenous immunoglobulins, or rituximab, they manifested persistent neurologic deficits and relapsing signs. Treatment with rituximab in combination with intravenous immunoglobulin, however, resulted in significant longterm clinical improvement.

Sjögren-Larsson syndrome: motor performance and everyday functioning in 17 patients.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive neurometabolic disorder characterized by spasticity, learning disability, and ichthyosis. To our knowledge, there is no detailed report in the literature concerning the functional consequences of SLS. Therefore, we performed a cross-sectional study of motor performance and everyday functioning in 17 patients with this rare disorder. Nine female and eight male patients with SLS (age range 1-35y) were investigated. Data were obtained by structured interview with parents and patients with SLS, a telephone-conducted questionnaire, and physical examination. Motor performance was measured by the Gross Motor Function Measure; everyday functioning was assessed using the Pediatric Evaluation of Disability Inventory and the Vineland Adaptive Behavior Scale. In most patients, spasticity was bilaterally present in hamstrings, hip adductors, and gastrocnemic muscles. All participants above 7 years had contractures in the lower extremities. Limitations were present in all gross motor dimensions, except for lying and rolling. Participants had developmental ages far below their chronological age. This study revealed that patients with SLS have limitations in gross motor performance. Although some patients can reach a certain level of independence, most have activity limitations and restrictions in their participation in society.

Behavioral treatment of drooling: a methodological critique of the literature with clinical guidelines and suggestions for future research.

Many children with mental retardation and developmental disabilities suffer from the consequences of chronic drooling. Behavioral treatment for drooling should be considered before other, more intrusive treatments such as medication and surgery are implemented. However, empirical studies on behavioral procedures are scarce. This article reviews 19 behavioral studies published since 1970. Treatment procedures are (a) instruction, prompting, and positive reinforcement; (b) negative social reinforcement and declarative procedures; (c) cueing techniques; and (d) self-management procedures. Although these procedures yield positive results, critical examination of experimental methodology of the studies reveals several methodological shortcomings. Guidelines for clinical use of behavioral treatment for drooling are presented, and recommendations are given for future research in this area.